Categories
Nevin Manimala Statistics

Repurposing anti-osteoporosis drugs for autoimmune diseases: A two-sample Mendelian randomization study

Heliyon. 2024 Jul 11;10(14):e34494. doi: 10.1016/j.heliyon.2024.e34494. eCollection 2024 Jul 30.

ABSTRACT

BACKGROUND: Despite the increasing availability of therapeutic drugs for autoimmune diseases, many patients still struggle to achieve their treatment goals. Our aim was to identify whether drugs originally used to treat bone density could be applied to the treatment of autoimmune diseases through Mendelian randomization (MR).

METHODS: Using summary statistics from genome-wide association studies, we used a two-sample MR design to estimate the correlation between autoimmune diseases and BMD-related drug targets. Data from the DrugBank and ChEMBL databases were used to identify the drug targets of anti-osteoporosis medications. The Wald ratio test or inverse-variance weighting method was used to assess the impact of genetic variation in drug target(s) on autoimmune disease therapy.

RESULTS: Through our analysis, we discovered a negative correlation between genetic variability in a specific gene (ESR1) in raloxifene/colecalciferol and various autoimmune disorders such as ankylosing spondylitis, endometriosis, IgA nephropathy, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, and type 1 diabetes.

CONCLUSION: These results indicate a possible link between genetic differences in the drug targeting ESR1 and susceptibility to autoimmune disorders. Hence, our study offers significant support for the possible use of drugs targeting ESR1 for the management of autoimmune disorders. MR and drug repurposing are utilized to investigate the relationship between autoimmune diseases and bone mineral density, with a focus on ESR1.

PMID:39130432 | PMC:PMC11315135 | DOI:10.1016/j.heliyon.2024.e34494

Categories
Nevin Manimala Statistics

Enhancing spatio-temporal environmental analyses: A machine learning superpixel-based approach

Heliyon. 2024 Jul 16;10(14):e34711. doi: 10.1016/j.heliyon.2024.e34711. eCollection 2024 Jul 30.

ABSTRACT

The progressive evolution of the spatial and temporal resolutions of Earth observation satellites has brought multiple benefits to scientific research. The increasing volume of data with higher frequencies and spatial resolutions offers precise and timely information, making it an invaluable tool for environmental analysis and enhanced decision-making. However, this presents a formidable challenge for large-scale environmental analyses and socioeconomic applications based on spatial time series, often compelling researchers to resort to lower-resolution imagery, which can introduce uncertainty and impact results. In response to this, our key contribution is a novel machine learning approach for dense geospatial time series rooted in superpixel segmentation, which serves as a preliminary step in mitigating the high dimensionality of data in large-scale applications. This approach, while effectively reducing dimensionality, preserves valuable information to the maximum extent, thereby substantially enhancing data accuracy and subsequent environmental analyses. This method was empirically applied within the context of a comprehensive case study encompassing the 2002-2022 period with 8-d-frequency-normalized difference vegetation index data at 250-m resolution in an area spanning 43,470 km2. The efficacy of this methodology was assessed through a comparative analysis, comparing our results with those derived from 1000-m-resolution satellite data and an existing superpixel algorithm for time series data. An evaluation of the time-series deviations revealed that using coarser-resolution pixels introduced an error that exceeded that of the proposed algorithm by 25 % and that the proposed methodology outperformed other algorithms by more than 9 %. Notably, this methodological innovation concurrently facilitates the aggregation of pixels sharing similar land-cover classifications, thus mitigating subpixel heterogeneity within the dataset. Further, the proposed methodology, which is used as a preprocessing step, improves the clustering of pixels according to their time series and can enhance large-scale environmental analyses across a wide range of applications.

PMID:39130414 | PMC:PMC11315160 | DOI:10.1016/j.heliyon.2024.e34711

Categories
Nevin Manimala Statistics

Integrative analyses of genes associated with oxidative stress and cellular senescence in triple-negative breast cancer

Heliyon. 2024 Jul 16;10(14):e34524. doi: 10.1016/j.heliyon.2024.e34524. eCollection 2024 Jul 30.

ABSTRACT

BACKGROUND: Oxidative stress and cellular senescence (OSCS) have great impacts on the occurrence and progression of triple-negative breast cancer (TNBC). This study was intended to construct a prognostic model based on oxidative stress and cellular senescence related difference expression genes (OSCSRDEGs) for TNBC.

METHODS: The Cancer Genome Atlas (TCGA) databases and two Gene Expression Omnibus (GEO) databases were used to identify OSCSRDEGs. The relationship between OSCSRDEGs and immune infiltration was examined using single-sample gene-set enrichment analysis (ssGSEA), ESTIMATE, and the CIBERSORT algorithm. Least absolute shrinkage and selection operator (LASSO) regression analyses, Cox regression and Kaplan-Meier analysis were employed to construct a prognostic model. Receiver operating characteristic (ROC) curves, nomograms, and decision curve analysis (DCA) were used to evaluate the prognostic efficacy. Gene Set Enrichment Analysis (GSEA) Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to explore the potential functions and mechanism.

RESULTS: A comprehensive analysis identified a total of 27 OSCSRDEGs, out of which 15 genes selected for development of a prognostic model. A high degree of statistical significance was observed for the riskscores derived from this model to accurately predict TNBC Overall survival. The decision curve analysis (DCA) and ROC curve analysis further confirmed the superior accuracy of the OSCSRDEGs prognostic model in predicting efficacy. Notably, the nomogram analysis highlighted that DMD exhibited the highest utility within the model. In comparison between high and low OSCScore groups, the infiltration abundance of immune cells was statistically different in the TCGA-TNBC dataset.

CONCLUSION: These studies have effectively identified four essential OSCSRDEGs (CFI, DMD, NDRG2, and NRP1) and meticulously developed an OSCS-associated prognostic model for individuals diagnosed with TNBC. These discoveries have the potential to significantly contribute to the comprehension of the involvement of OSCS in TNBC.

PMID:39130410 | PMC:PMC11315143 | DOI:10.1016/j.heliyon.2024.e34524

Categories
Nevin Manimala Statistics

Statistical assessment of natural radioactivity, radon activity, and associated radiological exposure due to artisanal mining in Atiwa West district of the Eastern region, Ghana

Heliyon. 2024 Jul 17;10(14):e34705. doi: 10.1016/j.heliyon.2024.e34705. eCollection 2024 Jul 30.

ABSTRACT

The activity concentration of natural radionuclides, radon activity concentration, mass and area exhalation rates have been studied in soils from gold mining communities in Atiwa West district. The natural radionuclides were determined by gamma ray spectrometry method while radon concentrations were measured using CR-39 detectors. The mean activity concentrations were found to be 26.9 ± 1.7 Bq/kg, 57.5 ± 3.6 Bq/kg, 237.5 ± 17.6 Bq/kg and 560.0 ± 54 Bq/m3 for Ra-226, Th-232, K-40 and Rn-222 respectively. The evaluated mass exhalation rates ranged from 2.8 ± 0.3 to 6.5 ± 0.7 × 10-5 Bq/kg/h while the area exhalation rates were from 0.8 ± 0.09 to 2.0 ± 0.21 × 10-3 Bq/m2/h. Some mining and farming areas recorded high exhalation rates indicating that the use of soils as building materials from such areas could pose a level of radiation hazard to the population. The evaluated radiological risks were below reference levels. A good linear correlation was observed between Ra-226 and Rn-222 activity concentrations and in the investigated soils. The Pearson correlation coefficient, cluster analysis and principal component analysis were used to study the relationship between the determined parameters of the study.

PMID:39130404 | PMC:PMC11315202 | DOI:10.1016/j.heliyon.2024.e34705

Categories
Nevin Manimala Statistics

Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study

Indian J Crit Care Med. 2024 Jun;28(6):581-586. doi: 10.5005/jp-journals-10071-24734.

ABSTRACT

AIMS AND BACKGROUND: In postoperative patients in the intensive care units (ICUs), not only analgesics are needed but also sedation so that the patient can remain calm during treatment, especially patients with mechanical ventilation. By using the measurement parameters of the quantum consciousness index (qCON) and quantum noxious index (qNOX) in measuring the depth of sedation and adequacy of analgesics, the use of subdose ketamine instead of fentanyl and midazolam as sedative, analgesic agents can be performed as a new alternative to nociceptive monitoring methods with more objective results. This study aims to obtain results of comparing qCON and qNOX in postoperative patients by administering subdose ketamine compared with a combination of fentanyl and midazolam in RSUP Haji Adam Malik Medan.

MATERIALS AND METHODS: A randomized clinical trial with a double-blind approach has been used in this study. A total of 44 experimental samples were gathered and randomly split into two groups after meeting the criteria for inclusion. Group A administered a ketamine subdose, whereas Group B administered a mixture of fentanyl and midazolam. The research data obtained were tested using Statistical Product and Science Service (SPSS).

RESULTS: There were differences in the median, minimum, and maximum values of qCON and qNOX in the groups given subdose ketamine and fentanyl and midazolam, but these were not statistically significant (p > 0.05) at T0, T1, and T2.

CONCLUSION: Administering a subdose of ketamine can provide sedation and analgesia comparable to fentanyl and midazolam.

HOW TO CITE THIS ARTICLE: Masharto AR, Lubis AP, Bangun CG, Wahyuni AS. Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study. Indian J Crit Care Med 2024;28(6):581-586.

PMID:39130399 | PMC:PMC11310667 | DOI:10.5005/jp-journals-10071-24734

Categories
Nevin Manimala Statistics

Is “Less be More” Still a Valid Concept in Intensive Care? A Review of Critical Care Randomized Clinical Trials from the New England Journal of Medicine

Indian J Crit Care Med. 2024 Jun;28(6):533-551. doi: 10.5005/jp-journals-10071-24717.

ABSTRACT

The concept of “Less is more” has been gaining increasing awareness and acceptance in Critical Care. In 2017, we attempted to systematically answer the question “Can less be more in intensive care” with empirical data. We reviewed all the critical care randomized clinical trials (RCTs) between 1 January 2008 and 5 October 2016 in the New England Journal of Medicine (NEJM). This article attempts to repeat the earlier exercise using data from 5 October 2016 to 31 December 2023. This analysis of critical care RCTs in the NEJM has shown three findings. Approximately three-quarter of RCTs in critical care in the NEJM between 2008 and 2023 failed to show benefit or harm. In the years 2008-2016, patients in the intervention cohort had a higher mortality compared to controls, but in the years 2016-2023, the difference in overall mortality in patients in the intervention and control arms was not statistically significant. Compared to the years 2008-2016, in the years from 2016 to 2023, the number of RCTs showing harm decreased and those showing benefit increased.

HOW TO CITE THIS ARTICLE: Kapadia F, Bharadwaj S, Sharma R. Is “Less be More” Still a Valid Concept in Intensive Care? A Review of Critical Care Randomized Clinical Trials from the New England Journal of Medicine. Indian J Crit Care Med 2024;28(6):533-551.

PMID:39130397 | PMC:PMC11310669 | DOI:10.5005/jp-journals-10071-24717

Categories
Nevin Manimala Statistics

Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial

Indian J Crit Care Med. 2024 Jun;28(6):587-594. doi: 10.5005/jp-journals-10071-24737.

ABSTRACT

AIM AND BACKGROUND: Sarcopenia is a substantial contributor to intensive care unit (ICU)-acquired weakness and is associated with significant short- and long-term outcomes. It can, however, be mitigated by providing appropriate nutrition. Indirect calorimetry (IC) is believed to be the gold standard in determining caloric targets in the dynamic environment of critical illness. We conducted this study to compare the effect of IC vs weight-based (25 kcal/kg/day) feeding on quadriceps muscle thickness (QMT) by ultrasound in critically ill patients.

MATERIALS AND METHODS: A prospective study was conducted on 60 mechanically ventilated patients randomized to two groups [weight-based equation (WBE) group or the IC group] in medical ICU after obtaining institutional ethics committee approval, and fed accordingly. The right QMT measurement using ultrasound and caloric targets were documented on day 1, 3 and 7 and analyzed statistically. The IC readings were obtained from the metabolic cart E-COVX ModuleTM.

RESULTS: The baseline demographics, APACHE-II, NUTRIC score, and SOFA scores on day 1, 3, and 7 were comparable between the two groups. The resting energy expenditure (REE) obtained in the IC group was significantly less than the WBE energy targets and the former were fed with significantly less calories. A significantly less percent reduction of QMT in the IC group compared with the WBE group was observed from day 1 to day 3, day 3 to day 7, and day 1 to day 7.

CONCLUSION: From our study, we conclude that IC-REE-based nutrition is associated with lesser reduction in QMT and lesser calories fed in critically ill mechanically ventilated patients compared from WBE. CTRI registration-CTRI/2023/01/049119.

HOW TO CITE THIS ARTICLE: Chandrasekaran A, Pal D, Harne R, Patel SJ, Jagadeesh KN, Pachisia AV, et al. Comparison between Effect of Indirect Calorimetry vs Weight-based Equation (25 kcal/kg/day)-guided Nutrition on Quadriceps Muscle Thickness as Assessed by Bedside Ultrasonography in Medical Intensive Care Unit Patients: A Randomized Clinical Trial. Indian J Crit Care Med 2024;28(6):587-594.

PMID:39130394 | PMC:PMC11310671 | DOI:10.5005/jp-journals-10071-24737

Categories
Nevin Manimala Statistics

Increasing the fracture strength of MOD restorations with Ribbond fibers

J Clin Exp Dent. 2024 Jun 1;16(6):e707-e713. doi: 10.4317/jced.61608. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: The aim of this study was to compare the fracture strength of two different Ribbond Fiber (Ribbond, Ribbond Inc., Seattle, WA, USA) restoration strategies in 5 mm deep standardized MOD cavities without interaxial dentin.

MATERIAL AND METHODS: 34 extracted human molars were randomly divided into two groups and restored as follows: Group 1 restoration with Ribbond Fiber placed at the cavity floor incorporated in Estelite Bulk-Fill Flow Universal composite (Tokuyama Dental Corporation Inc., Tokyo, Japan); Group 2 restoration with RF placed at 3 mm from the occlusal plane over a 2mm layer of Estelite Bulk-Fill Flow. The occlusal plane in both groups was restored with Ceram.x Spectra ST (Dentsply Sirona, Ballantyne Corporate Pl, Charlotte, NC, USA). The restored teeth were subjected to thermal cycling by immersing them for 30 seconds in hot water (55±2°C) followed by 30 seconds in cold water (5±2°C), for 2000 cycles.Their fracture strength was then evaluated using an Instron device. Data were analyzed with Two-sample T Test statistical test to compare fracture strength among groups. Finally, a descriptive analysis of the failure location was performed.

RESULTS: A statistically significant difference was found between groups 1 and 2 (P<0.001) in terms of fracture strength. Group 2 exhibited a higher percentage of recoverable fractures compared to group 1. Group 1 had a mean fracture load of 833N and a SD of 248 while group 2 had a mean fracture load of 1286N and SD of 447.

CONCLUSIONS: RF placed at 3 mm depth from the occlusal plane, on a 2 mm layer Estelite Bulk-Fill Flow Universal composite (Tokuyama Dental Corporation Inc., Tokyo, Japan) contributes to improve fracture resistance in vital teeth without interaxial dentin and reduces the risk of non-recoverable fractures compared to when it is placed at a 5 mm depth. Key words:Ribbond fiber, composite restoration, fracture resistance, Instron machine.

PMID:39130368 | PMC:PMC11310981 | DOI:10.4317/jced.61608

Categories
Nevin Manimala Statistics

Influence of root canal taper on the measurement of two different electronic apex locators

J Clin Exp Dent. 2024 Jun 1;16(6):e733-e739. doi: 10.4317/jced.61352. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: This research aimed to analyze the influence of root canal taper on the accuracy of two Electronic Apex Locators (EALs).

MATERIAL AND METHODS: Twenty-five disto-vestibular roots from extracted human upper molars belonging to the tooth bank were used in this study. To determine the File Position (FP), access was made using a spherical diamond tip #1014, and the crowns were sectioned using a diamond tip #3080. The initial anatomic file used was a size K #10, which was introduced into the root canal until its tip was visualized (foraminal patency) with the aid of a clinical microscope (16X magnification). Teeth without foraminal patency and calcifications were excluded from the study. Odontometric readings were performed using two different EALs (Root ZX II and Romiapex A-15), considering the electronic reference point 0.0 (apex) for each device. All measurements were taken in triplicate, and the arithmetic mean of the three values was used. Digital calipers were used to record the measurements, which were then entered into an Excel spreadsheet. After visual verification using file K #10, the canals were instrumented with a #25.01 file to standardize the apical region, then successively instrumented with files #25.02, #25.04, #25.06, #25.08, #25.10, and #25.12, with electronic odontometry checked after each instrumentation using #25.02. Measurement 0.0 was adopted, with error margins of ±0.5 and ±1.0. Discrepancies between visual and electronic readings were statistically analyzed using ANOVA and Bonferroni tests, with significance considered when P<0.05.

RESULTS: Using the 0.0 mark and a ±1.0 error margin, it was observed that readings from the devices were similar in canals with different tapers (P>0.05), showing a tendency towards underestimation. However, when using the measurement variation margin of ±0.50, a statistically significant difference was found in the Romiapex A-15 group (P=0.0248) when comparing the results of the two EALs.

CONCLUSIONS: Therefore, it was concluded that the canal taper did not significantly influence the accuracy of the evaluated EALs, using the reference point 0.0. When using the ±0.5 variation margin, the Romiapex A-15 device showed greater accuracy, and finally, at the ±1.0 error margin, both EALs exhibited excellent precision. Key words:Endodontics, Odontometry, Eletronic Apex Locator, Root Canal Preparation.

PMID:39130363 | PMC:PMC11310975 | DOI:10.4317/jced.61352

Categories
Nevin Manimala Statistics

The role of protective liners and glass ionomer in managing pulp temperature during light curing

J Clin Exp Dent. 2024 Jun 1;16(6):e749-e754. doi: 10.4317/jced.61703. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: To evaluate the thermal insulation of protective liners and glass ionomer cement during light-curing procedures.

MATERIAL AND METHODS: Human third molars underwent Class I preparations with dimensions 5 mm long × 4 mm wide × 4 mm deep in a standardized manner ensured a consistent ±0.5 mm dentin thickness at the pulpal floor. The teeth were attached to a customized oral cavity chamber simulator with a circulating bath at a standardized temperature of 34.2 ± 1oC. The temperature variations at the pulpal floor were captured in real-time by video using an infrared thermal camera (FLIR ONE Pro, FLIR Systems). The materials evaluated were: Dycal (Dentsply), TheraCal LC (Bisco), Activa (Pulpdent), and Fuji II LC (GC). All light-activation procedures were performed with the same light-curing unit (Valo Grand, Ultradent) in standard mode, 1000 mW/cm2, and time of exposure following manufacturer instructions. A power analysis was conducted to determine the sample size considering a minimal power of 0.8, with α=0.05. Statistical analyses were performed using ANOVA and Tukey’s test for multiple comparisons.

RESULTS: The temperature at the pulpal floor increased above the 5.5 ºC safety threshold difference for clinical scenarios tested. None of the materials provided proper thermal insulation for light-curing procedures (p = 0.25). The higher the number of light-cured steps, the longer the pulp remained above the 5.5 ºC temperature threshold.

CONCLUSIONS: The materials tested provided improper thermal insulation (Δ > 5.5 ºC). Thus, prolonged or multiple light-curing exposures can be harmful to the pulp tissues. Therefore, for indirect pulpal capping procedures, self-cured materials or a reduced number of steps requiring light curing must be adopted to reduce the amount of time the pulp remains above the 5.5 ºC safety temperature threshold. Key words:Dental Pulp Capping, Calcium hydroxide, Bioactive, Thermal Damage.

PMID:39130362 | PMC:PMC11310984 | DOI:10.4317/jced.61703